biostudies-literatureCosta KMU.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA)Intramural NIH HHSDeutsche ForschungsgemeinschaftAlexander von Humboldt-StiftungU.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse107-115https://www.ebi.ac.uk/biostudies/studies/S-EPMC9839657biostudies-literatureUnknown26(1)We use mental models of the world-cognitive maps-to guide behavior. The lateral orbitofrontal cortex (lOFC) is typically thought to support behavior by deploying these maps to simulate outcomes, but recent evidence suggests that it may instead support behavior by underlying map creation. We tested between these two alternatives using outcome-specific devaluation and a high-potency chemogenetic approach. Selectively inactivating lOFC principal neurons when male rats learned distinct cue-outcome associations, but before outcome devaluation, disrupted subsequent inference, confirming a role for the lOFC in creating new maps. However, lOFC inactivation surprisingly led to generalized devaluation, a result that is inconsistent with a complete mapping failure. Using a reinforcement learning framework, we show that this effect is best explained by a circumscribed deficit in credit assignment precision during map construction, suggesting that the lOFC has a selective role in defining the specificity of associations that comprise cognitive maps.Nature neuroscienceThe role of the lateral orbitofrontal cortex in creating cognitive maps.PMC9839657da000587ZIA DA000587MA 8509noneCosta KMScholz RSchoenbaum GGardner MPHMoreno-Castilla PLloyd KDayan PfalseThe role of the lateral orbitofrontal cortex in creating cognitive maps.We use mental models of the world-cognitive maps-to guide behavior. The lateral orbitofrontal cortex (lOFC) is typically thought to support behavior by deploying these maps to simulate outcomes, but recent evidence suggests that it may instead support behavior by underlying map creation. We tested between these two alternatives using outcome-specific devaluation and a high-potency chemogenetic approach. Selectively inactivating lOFC principal neurons when male rats learned distinct cue-outcome associations, but before outcome devaluation, disrupted subsequent inference, confirming a role for the lOFC in creating new maps. However, lOFC inactivation surprisingly led to generalized devaluation, a result that is inconsistent with a complete mapping failure. Using a reinforcement learning framework, we show that this effect is best explained by a circumscribed deficit in credit assignment precision during map construction, suggesting that the lOFC has a selective role in defining the specificity of associations that comprise cognitive maps.2023-01-01T00:00:00Z2023 Jan2024-11-20T05:35:54.69Z2024-11-20T05:35:54.69ZS-EPMC98396573655029010.1038/s41593-022-01216-0